Abstract Number: PB0984
Meeting: ISTH 2021 Congress
Background: In-depth platelet reactivity testing requires dedicated equipment, personnel and time. Therefore, large studies are rarely conducted and there is a paucity of studies comparing platelet assays.
Aims: In the most recent Framingham Heart Study exam, standard measures of platelet function were collected with an aim to identify correlations among these assays.
Methods: Informed consent was obtained, and the study was approved by the Boston University Medical Center institutional review board. Fasting blood was drawn from participants (self-declared European ancestry, N=3140, 46.4% male, 54.5±9.0 years) into sodium citrate or hirudin anti-coagulant. Citrated blood was centrifuged to obtain platelet-rich plasma (PRP). Five platelet reactivity assays (Table) were performed in whole blood or PRP. Aspirin use was defined as arachidonic acid (AA) final aggregation <40% in LTA. Correlation matrices were constructed for the platelet assays. In addition, platelet responses were ranked into quintiles and Cohen’s Kappa (κ) test was performed to assess the correspondence between the lowest and highest responders for each assay.
Results: Aspirin was associated with a high correlation between AA-mediated responses in LTA and Multiplate. When aspirin takers (N=681) were removed, this correlation was significantly reduced. Strong intra-assay correlation was seen in all assays, particularly in Multiplate (ADP vs TRAP area under the curve [AUC], Pearson’s r=0.619). Moderate inter-assay correlation was observed between epinephrine AUC responses in LTA and Optimul (r=0.418). Furthermore, female sex increased platelet reactivity in nearly all traits (e.g. Multiplate ADP AUC; r=0.281). Finally, we showed that highest 20% of responders to ristocetin were also high responders to TRAP-6 amide (LTA AUC; κ=0.653) and lowest responders to these agonists were also correlated (κ=0.583).
|Multiplate impedance aggregometry||Total Thrombus formation Analysis System (T-TAS)||Flow cytometry||Light transmission aggregometry (LTA)||Optimul aggregometry|
|Arachidonic acid (AA)||0.5mM||1.6mM||0.03mM, 0.06mM, 0.11mM, 0.19mM, 0.33mM, 0.57mM, 1mM|
|ADP||3.19μM||20μM||0.95μM, 1.82μM, 5.71μM||0.005μM,0.02μM, 0.10μM, 0.44μM, 1.98μM, 8.89μM, 40μM|
|Collagen||0.061mg/mL||Type I||0.19mg/mL||0.01μg/ml, 0.04μg/ml, 0.16μg/ml, 0.62μg/ml, 2.5μg/ml, 10μg/ml, 40μg/ml|
|Epinephrine||100μM||0.0004μM, 0.001μM, 0.01μM, 0.06μM, 0.33μM, 1.82μM, 10μM|
|Ristocetin||1.15mg/mL||1.5mg/mL||0.14mg/ml, 0.24mg/ml, 0.43mg/ml, 0.75mg/ml, 1.31mg/ml, 2.29mg/ml, 4mg/ml|
|TRAP-6 amide||4.48μM||15μM||0.03μM, 0.11μM, 0.36μM, 1.1μM, 3.79μM, 12.3μM, 40μM|
|U46619||0.005μM, 0.02μM, 0.10μM, 0.44μM, 1.98μM, 8.89μM, 40μM|
Conclusions: Caution must be taken in extrapolating responses between assay types, even for the same agonist. The dynamics of each assay must be considered when choosing or interpreting the results of a platelet assay.
To cite this abstract in AMA style:Chan MV, Chen M-, Thibord F, Lachapelle A, Grech J, Armstrong PCJ, Warner TD, Johnson AD. A comparison of Five Platelet Reactivity Tests in Over 3,000 Participants of the Framingham Heart Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/a-comparison-of-five-platelet-reactivity-tests-in-over-3000-participants-of-the-framingham-heart-study/. Accessed December 7, 2021.
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